Mitochondrial toxicity of triclosan on mammalian cells

Charmaine Ajao; Maria A Andersson; Vera V Teplova; Szabolcs Nagy; Carl G Gahmberg; Leif C Andersson; Maria Hautaniemi; Balazs Kakasi; Merja Roivainen; Mirja Salkinoja-Salonen

doi:10.1016/j.toxrep.2015.03.012

Mitochondrial toxicity of triclosan on mammalian cells

Toxicol Rep. 2015 Apr 7:2:624-637. doi: 10.1016/j.toxrep.2015.03.012. eCollection 2015.

Authors

Affiliations

¹ Department of Food and Environmental Sciences, Haartman Institute, University of Helsinki, POB 56, FI-00014, Finland.
² Institute of Theoretical and Experimental Biophysics, RAS, Puschino, Moscow Region, Russia.
³ Department of Animal Science and Animal Husbandry, University of Pannonia, Georgikon Faculty, Deak F. u.,16, H8360 Keszthely, Hungary.
⁴ Dept. of Bio- and Environmental Sciences, Haartman Institute, University of Helsinki, FI-00014, Finland.
⁵ Dept. of Pathology, Haartman Institute, University of Helsinki, FI-00014, Finland.
⁶ Finnish Food Safety Authority (EVIRA), Research and Laboratory Department, Veterinary Virology Research Unit, Mustialankatu 3, FI 00790 Helsinki, Finland.
⁷ Institute of Environmental Sciences, University of Pannonia, Egyetem u. 10, H-8200 Veszprem, Hungary.
⁸ National Institute for Health and Welfare, Department of Virology, Mannerheimintie 166, 00300 Helsinki, Finland.

Abstract

Effects of triclosan (5-chloro-2'-(2,4-dichlorophenoxy)phenol) on mammalian cells were investigated using human peripheral blood mono nuclear cells (PBMC), keratinocytes (HaCaT), porcine spermatozoa and kidney tubular epithelial cells (PK-15), murine pancreatic islets (MIN-6) and neuroblastoma cells (MNA) as targets. We show that triclosan (1-10 μg ml^-1) depolarised the mitochondria, upshifted the rate of glucose consumption in PMBC, HaCaT, PK-15 and MNA, and subsequently induced metabolic acidosis. Triclosan induced a regression of insulin producing pancreatic islets into tiny pycnotic cells and necrotic death. Short exposure to low concentrations of triclosan (30 min, ≤1 μg/ml) paralyzed the high amplitude tail beating and progressive motility of spermatozoa, within 30 min exposure, depolarized the spermatozoan mitochondria and hyperpolarised the acrosome region of the sperm head and the flagellar fibrous sheath (distal part of the flagellum). Experiments with isolated rat liver mitochondria showed that triclosan impaired oxidative phosphorylation, downshifted ATP synthesis, uncoupled respiration and provoked excessive oxygen uptake. These exposure concentrations are 100-1000 fold lower that those permitted in consumer goods. The mitochondriotoxic mechanism of triclosan differs from that of valinomycin, cereulide and the enniatins by not involving potassium ionophoric activity.

Keywords: Acidosis; BCF, bioconcentration factor; EC50, concentration that diminishes the respective vitality parameter by ≥50%; Electric transmembrane potential; Glycolysis; HaCaT, a spontaneously immortalized (non-neoplastic) keratinocyte cell line; JC-1, 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolyl-carbocyanine iodide; MIC, minimal inhibitory concentration; MIN-6, a murine pancreatic beta cell line; MNA, a murine neuroblastoma cells; Oxidative phosphorylation; PBMC, monocyte-enriched peripheral blood mononuclear cells; PI, propidium iodide; PK-15, a porcine kidney tubular epithelial cell line; PN, pyridine nucleotides; RLM, rat liver mitochondria; Sperm motility; TPP+, tetraphenylphosphonium; Uncoupler; ΔΨ, electric transmembrane potential; ΔΨm, membrane potential of the mitochondrial membrane; ΔΨp, membrane potential of the plasma membrane.